The goal of our project is to investigate the etiology of facial clefts by analyzing family data for the Hispanic population treated by the Cleft Palate Service of Rancho Los Amigos Hospital, Los Angeles County, California. We have computerized the patient file for the Cleft Palate Service and have over 700 patients available for study. Excellent information is available on clefting status directly from the records. Family history and ethnic background are being verified by family interview. The initial goal of 200 Hispanic families with verified data has been met and genetic analyses are on-going at this time. In addition we have collected dermatoglyphics data probands and their relatives and these data are being subjected analysis for asymmetry. Recent analyses by ourselves and others (Chung et al, Am. J. Hum. Genet., 1986) have confirmed an autosomal recessive clefting gene in a sample from Denmark. In addition Chung's group found only evidence for a multifactorial etiology in a sample from Japan. Given this new evidence for genetic heterogeneity and the fact that our sample from RLAH is twice the size we predicted, our renewal focuses on the genetic heterogeneity of clefting. We will test the hypothesis that an autosomal recessive form of clefting is segregating in a portion of the families in our Hispanic population. We feel this is true based on the initial appraisal of the pedigrees with positive family history. We will confirm the frequency of clefting types in the Hispanic population by determining if referral bias or some other irrelevant factor accounts for the increases frequency of cleft lip with cleft palate in our sample. The sex ratio and bilateral vs. unilateral frequencies match those predicted from observations in other populations. We will carry out genetic linkage and mapping studies on the families with positive family history. The specific goals are to determine if the X-linked form of cleft palate detected in an Icelandic population occurs in our population and to determine if the locus for van der Woude syndrome (currently being mapped in Caucasians) is the same in Hispanics and Blacks.